In the next grant period, we will continue our studies on macromolecular synthesis in ascites L1210 cells with Miracil D and Hycanthone with emphasis on selective inhibition and chain length of nucleolar, nucleoplasmic, and cytoplasmic RNA. In addition, the effects on DNA sedimentation, on nuclear RNA polymerase, on uridine and thymidine nucleotides in the acid-soluble pools, and on nuclear acidic proteins will be examined to gain a clearer understanding of the mechanism to account for the chemotherapeutic properties of the compounds. As time progresses, these studies will be extended to other compounds (formycin, daunomycin, sangivamycin, and bleomycin) which were cited in the original grant and which are carcinostatic, but whose modes of action are probably different. Studies of the past grant period have shown that Miracil D and its analogs or metabolites affect DNA synthesis more markedly than RNA synthesis in ascites L1210 cells. Under the conditions studied (concentrations of Miracil D or Hycanthone which would produce a 50 percent inhibition of incorporation of RNA or DNA precursors after 20 minutes), the rate of RNA synthesis was restored to that of uninhibited samples subjected to similar manipulations. Inhibition of DNA synthesis by either Miracil D or Hycanthone under similar conditions as for RNA was only partially reversible. In studies on RNA synthesis in whole cells, there was at all times studied a peak of small molecular weight RNA, and that as the time of incubation was extended there was a gradual increase in radioactivity in the S54, S23, and S18 regions. At all times studied, Miracil D inhibited the small molecular weight RNA and after 30 minutes inhibition was noted in the S45 region and after 60 and 90 minutes there were marked inhibitions in all RNA formed. o